1. Functional characterisation of long intergenic non-coding RNAs through genetic interaction profiling in Saccharomyces cerevisiae
- Author
-
Kyriakou, DImitris, Stavrou, Emmanouil, Demosthenous, Panayiota, Angelidou, Georgia, San Luis, B. -J, Boone, Charles M., Promponas, Vasilis J., Kirmizis, Antonis, Promponas, Vasilis J. [0000-0003-3352-4831], and Kirmizis, Antonis [0000-0002-3748-8711]
- Subjects
0301 basic medicine ,Saccharomyces cerevisiae Proteins ,Physiology ,Saccharomyces cerevisiae ,Genomics ,Plant Science ,Genome ,General Biochemistry, Genetics and Molecular Biology ,Long intergenic non-coding RNAs ,Transcriptome ,Synthetic genetic array ,03 medical and health sciences ,Structural Biology ,DNA, Fungal ,Gene ,Telomerase ,Ecology, Evolution, Behavior and Systematics ,Genetics ,biology ,Agricultural and Biological Sciences(all) ,Biochemistry, Genetics and Molecular Biology(all) ,Gene Expression Profiling ,Genetic interactions ,Cell Biology ,Telomere ,biology.organism_classification ,Gene expression profiling ,030104 developmental biology ,Exodeoxyribonucleases ,Gene Ontology ,RNA, Long Noncoding ,Genome, Fungal ,Stable unannotated transcripts ,General Agricultural and Biological Sciences ,Developmental Biology ,Biotechnology ,Research Article - Abstract
Background Transcriptome studies have revealed that many eukaryotic genomes are pervasively transcribed producing numerous long non-coding RNAs (lncRNAs). However, only a few lncRNAs have been ascribed a cellular role thus far, with most regulating the expression of adjacent genes. Even less lncRNAs have been annotated as essential hence implying that the majority may be functionally redundant. Therefore, the function of lncRNAs could be illuminated through systematic analysis of their synthetic genetic interactions (GIs). Results Here, we employ synthetic genetic array (SGA) in Saccharomyces cerevisiae to identify GIs between long intergenic non-coding RNAs (lincRNAs) and protein-coding genes. We first validate this approach by demonstrating that the telomerase RNA TLC1 displays a GI network that corresponds to its well-described function in telomere length maintenance. We subsequently performed SGA screens on a set of uncharacterised lincRNAs and uncover their connection to diverse cellular processes. One of these lincRNAs, SUT457, exhibits a GI profile associating it to telomere organisation and we consistently demonstrate that SUT457 is required for telomeric overhang homeostasis through an Exo1-dependent pathway. Furthermore, the GI profile of SUT457 is distinct from that of its neighbouring genes suggesting a function independent to its genomic location. Accordingly, we show that ectopic expression of this lincRNA suppresses telomeric overhang accumulation in sut457Δ cells assigning a trans-acting role for SUT457 in telomere biology. Conclusions Overall, our work proposes that systematic application of this genetic approach could determine the functional significance of individual lncRNAs in yeast and other complex organisms. Electronic supplementary material The online version of this article (doi:10.1186/s12915-016-0325-7) contains supplementary material, which is available to authorized users.
- Published
- 2016